We have several research objectives. Every normal subject excretes methylated purines, pyrimidines and some of their breakdown products. The Principal Investigator was able to demonstrate that these products originate from the normal turnover of tRNA. He also showed that tRNA modification and metabolism are aberrant in tumor tissue, and the rate of turnover of tRNA in tumor tissue is highly elevated. Consequently, cancer patients excrete elevated levels of modified nucleosides and products derived from them. The Principal Investigator and his collaborators have perfected a sensitive, accurate analytical procedure for the determination of modified nucleosides in one milliliter of spot samples of urine relative to the creatinine content. Some of these markers are significantly elevated in the urine of every cancer patient examined. It was found that the level of these excretion products returns to normal after surgery or effective chemotherapy and remains normal as long as the patient is in remission. Prior to observable relapse, the excretion becomes elevated again. We wish to extend these observations to explore the molecular mechanisms from which the elevated levels of the excretion products originate in tumor tissue. We also wish to investigate the molecular mechanism of the return of the excretion levels to normal soon after effective chemotherapy.